Devlopment And Treatment Of Colorectal Cancer Biology Essay

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Fundamentally cancer occurs from accumulated alterations in the genes which regulate cell proliferation and differentiation (Croce, 2008). Normal cells slowly and systemically replace dead ones, whereas cancer cells keep reproducing, and do not surrender to signals from body control (Cancer Research UK, 2010). Cancerous cells could invade nearby tissues, and even spread to other organs through lymph nodes or blood vessels, which might eventually lead to loss of adequate functions in the body system (Chang, Daly, & Elliott, 2006)

As the second most common cancer, colorectal cancer is a major medical issue in Australia (Portelli, 2008), with 13,500 new cases of colorectal cancer every year (Cancer Council Australia, 2010). In this report, I will present the pathophysiology and adjuvant chemotherapy of colorectal cancer, how the gastrointestinal system might be influenced by it, and how clinicians should assess subjective and objective data of patients in post-surgery care, regarding a 65 year old indigenous woman.

Pathophysiology of cancer

Development of colorectal cancer

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Colorectal cancer is a malignant neoplasm in the large intestine and generally limited locally for a long term before invasion and metastasis (The Cancer Council Australia & Australian Cancer Network, 2005). Adenomatous polyps on the wall of large intestine have possibility to grow into colorectal cancer and around 80% of tumours in the colon are developed through adenoma-carcinoma sequence over years (Kumar, Abbas, Fausto, & Aster, 2010). For instance, the loss of TSG on chromosome 5 or other in mucosa cells of the colon could lead normal epithelium to become hyperproliferative, making small, benign polyps. Further combinations of the loss of DNA methylation, activation of ras oncogene on chromosome 12, and loss of DCC on chromosome 18, transforms small polyps into larger benign polyps, or adenoma. On top of that, the loss of p53 TSG on chromosome 17 culminates in carcinoma (Marieb & Hoehn, 2010). Molecular alterations in the adenoma-carcinoma sequence are demonstrated in Figure 1 (Kumar, et al., 2010).

Additional mutations contribute to metastasis, in which cancerous cells travel to other body organs via lymphatic or blood vessels, forming secondary cancer masses (Chang, et al., 2006).

Intrusion into adjacent tissues and spreading to other organs differentiate cancer from benign neoplasm. Stage grouping of colorectal cancer according to the TNM (for tumours/nodes/metastasis) system is described in Table 1 (American Joint Committee on Cancer, 2009).

It is known that Stage 0 can be cured by cutting cancerous cells during a colonoscopy, but Stages I to III require much substantial surgical resection, while treatment for Stage IV focuses on the extension of patient's life through palliative chemotherapy and radiation therapy (National Institutes of Health, 2010). Mrs Lane's case seems to have progressed further than Stage II and be less than Stage IV, because treatment for Stage III usually involves colectomy with adjuvant chemotherapy.

Risk factors

Although most colorectal cancers are directly derived from adenomatous polyps as described in 1-1, many other factors also contribute to the formation of colorectal cancer. Risk factors other than polyps are as follows (Casciato & Lowitz, 1995):

Age: the risk of carcinoma of colon and rectum increases with age. Incidence rates per 100,000 in respect of ages and sexes in 2006, Australia are presented in Graph 1 (Australian Institute of Health and Welfare, 2010).

Diet: Excess intake of red meat and low intake of fibre may increase the risk of colorectal cancer.

Genetic factors: if a person has a relative with colorectal cancer, that person's risk is increasing. Specific inherited and/or acquired genetic mutations such as adenomatous polyposis coli gene or ras gene point mutation, also contribute to development of colorectal cancer.

Other factors: previous history of cancer, inflammatory bowel disease, smoking, heavy drinking, lack of physical activity and deficiency of Vitamin B6 intake are risk factors towards colorectal cancer.

Mrs Lane might be classified as a typical colorectal cancer patient, because she is a 65-year- old Australian. Australia is surely a high risk country and approximately one in 21 Australians develops colorectal cancer during their lifetime, with the risk soaring after 50 years of age (The Cancer Council Australia & Australian Cancer Network, 2005).

Signs and symptoms

Three main sets of common clinical manifestations of colorectal cancer are as follows (The Cancer Council Australia & Australian Cancer Network, 2005):

Rectal bleeding

Bowel or abdominal symptoms

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Iron deficiency anaemia

Obstruction from tumours suppressing colon wall could be included as symptoms (McCance, Huether, Brashers, & Rote, 2010). Additionally, patients may experience weight loss, since cancer cells generally exploit much energy from the body and patients usually lose appetite also. Particularly patients with right colonic carcinoma tend to demonstrate fatigue and weakness due to iron deficiency amenia (Kumar, et al., 2010).

Therefore, Mrs Lane's 9 kg loss in weight might be explained by decreased appetite and nutrients consumption by cancer cell which deprives the body of energy. Her abdominal pain could be contributed to the injury of intestinal tissue or bowel obstruction.

Chemotherapy

General principles of chemotherapy

More than 33% of colorectal cancer cases involve lymph nodes spreading, which is Stage III or further Stage, and more than 50% of these cases could reoccur the disease after initial surgery (Cancer Council Australia & Australian Cancer Network, 2005). Adjuvant chemotherapy is used to enhance survival after colorectal resection and decrease the possibilities of relapse or metastasis, especially for Stage III patients (Gee, 2009). There are many solid proofs that chemotherapy conferring patients with 5-fluorouracil (5-FU), the first-choice cytotoxic agent for colorectal cancer, improves survival. For example, a recent study involving 1,135 registered patients undergone colorectal resection shows that adjuvant chemotherapy can reduce the rate of cancer relapse and death after surgery by more than 30% (Poplin et al., 2005). Generally chemotherapy is carried out in multiple cycles: a cycle consists of a period of receiving drugs to kill cancer cells and a resting period to build up new healthy cells (United States National Cancer Institute, 2010).

How the chemotherapy works

In molecule level, chemotherapy works by disrupting the DNA in cells, preventing replication and reproduction (Chang, et al., 2006). While cancer cells divide fast, normal cells slowly substitute worn out ones via cell cycle of growing, dividing, and dying phases, and most normal cells in the body are not dividing at any given time. Therefore chemotherapy systematically targets cells dividing at the time.

Although there are several categories of anti-cancer drugs, for example, alkylating agents, topoisomerase inhibitors, anthracyclines, the most commonly used medicine for colorectal cancer is an antimetabolite: 5-FU (Chang, et al., 2006). The function of antimetabolites is basically to impede the use of a metabolite, which is an intermediate of metabolism and straightly related to the cell division cycle. To be specific, 5-FU can inhibit synthesis of pyrimidine thymidine, one of basic elements necessary to replicate DNA (Wilkes & Barton-Burke, 2006). The standard treatment for Duke's C cancer (cancer involving lymph nodes), for example, is administering the combination of 5-FU and leucovorin which enhances the function of 5-FU, over 6 months. Mrs. Lane's chemotherapy seems to follow this standard treatment, as her 26 cycle course might imply 26 weeks of cycles.

Side effects

However, there are several side effects of chemotherapy. First, because anti-cancer drugs are administered targeting to dividing cells, they are not only harmful to cancer cells but also to other normal body parts such as hair follicles, mucosal cells in the intestines, and bone marrow, where cells proliferate rapidly (Bullock, Manias, & Galbraith, 2007). Second, cancer cells could become resistant to anti-cancer drugs as their mutations go further (Chang, et al., 2006). Third, patients might become vulnerable to infection due to bone marrow suppression with lack of ability to produce adequate amount of leukocytes (Cao et al., 2008), particularly if 5-FU is administered with allopurinol (Tiziani, 2006). In addition, nausea and vomiting could occur to 30-50% of patients on the chemotherapy offered with 5-FU, resulting in poor nutrition (Wilkes & Barton-Burke, 2006). As chemotherapy is toxic in itself, it is critical that Mrs. Lane understand the adverse effects of it and build cooperative relationship with clinicians during treatment, to prevent any possible toxicity prior to further development.

Digestive system and colorectal cancer

Over view of digestive system

Digestive system consists of organs of the alimentary canal (mouth, oesophagus, stomach, small intestine and large intestine), and associated organs (liver, pancreas and gall bladder). Its main function is to provide body cells with nutrients. Because human body could not utilise the food taken directly, it needs to be broken down into smaller molecules, through gastrointestinal tract which is controlled by both intrinsic and autonomic nerve system, to ensure optimal functioning. Digestive processes are categorised as ingestion, propulsion, mechanical digestion, chemical digestion, absorption and defecation. The breif functions of each digestive organ are described as follows:

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Mouth

Oesophagus

Stomach

Small intestine

Largeintestine

While the small intestine absorbs most digested molecules of food (carbohydrates, protein, fats), vitamins, electrolytes, and 90% of water, the large intestine absorbs residual waters and electrolytes.

Hydrolysis, a catabolic process, (the chemical alteration of decomposition of a compound with water from mosby's dictionary) achieves chemical digestion.

How digestive system might be affected by colorectal cancer

Colorectal cancer could affect Mrs. Lane's digestive system in various ways according to following sequences.

Before treatment

Colorectal cancer could cause several disorders in digestive system, such as altered metabolism resulting from cancerous mutations (Locasale & Cantley, 2010) or possible weight loss and fatigue related with excessive energy expenditure by high metabolic rate of tumours (Ravasco, Monteiro-Grillo, & Camilo, 2007). In addition, active neoplastic tissues and intestinal lymphomas resulting from cancerous intrusion to lymph nodes might disrupt the absorptive function of colon (Bloch, 1990).

Post surgery status: formation of colostomy

Partial or total colon resection might produce severe loss of fluid and electrolytes (Bloch, 1990). Formation of colostomy might bear the risk for alterations of normal bowel function, such as diarrhoea and constipation (Doenges, Moorhouse, & Murr, 2008).

In the course of adjuvant chemotherapy

Chemotherapy might induce anorexia, nausea and/or vomiting (Wilkes & Barton-Burke, 2006). Each of them can cause excessive weight loss accompanied by imbalance of fluid and electrolytes (Luggen & Meiner, 2000).

Assessment of subjective and objective data in post-surgery care

Assessment in the course of chemotherapy

As mentioned in 2-3 and 3-2, chemotherapy could result in impaired immunocompetence and several disorders of gastrointestinal system. Therefore nurses should be able to evaluate abnormal signs and symptoms related to these problems in order to avoid further toxicities and relieve compromised situations.

Impaired immunocompetence

The lowest point of the white blood cell (WBC) count would be mainly assessed between 7 and 14 days after chemotherapy administration (Chang, et al., 2006). Normal ranges for WBC and absolute neutrophil count (ANC) are 4,500-9,000/mm³ and more than 2,000/mm³, respectively. If Mrs. Lane experiences pyrexia/rigor, erythema, swelling at any site with her WBC less than 3,000/mm³ and ANC less than 1,000/mm³, clinicians should consider the possibility of chemotherapy-induced neutropenia and hold myelosuppressive drugs (Wilkes & Barton-Burke, 2006).

Anorexia

In order to evaluate whether Mrs. Lane is with anorexia, clinicians should monitor her weight and present values of albumin and total protein, and compare them with normal weight and normal laboratory values (Wilkes & Barton-Burke, 2006). Keeping notes on dietary pattern changes and any allergic reactions to food taken would be helpful as well.

Vomiting and Nausea

Vomiting and Nausea could be one of the worst side effects of chemotherapy. Clinicians might address them by communicating with Mrs. Lane to assess the severity, incidence and frequency of them, and their effects on daily life (Chang, et al., 2006). Comparing Mrs. Lane's laboratory values of electrolytes with normal levels could be informative to determine the severity of vomiting (Wilkes & Barton-Burke, 2006). Appropriate antiemetic drugs taken before, during and after chemotherapy could relieve vomiting and nausea, and Mrs. Lane's response to antiemetics should be recorded (Luggen & Meiner, 2000).

Assessment regarding complications after colostomy

If Mrs. Lane's stoma is created from the ascending colostomy, the stool from it would be semi-liquid and include digestive enzymes that might be irritable to skin. Possible complications following formation of colostomy could include wound infections such as peristomal ulceration and intestinal obstruction (Ugolini et al., 2009). Nurses are supposed to take a role to detect the postoperative complications and provide patients with adequate interventions in time.

Wound infection

The signs and symptoms of wound infection usually appear in 3 to 4 days after surgery: fever, elevated WBC count, increasing pain, oedema continued after the initial swelling, and redness beyond the incision line (Black & Hawks, 2009).

Intestinal obstruction

If Mrs. Lane complains of cramping abdominal pain, nausea and vomiting, and abdominal distension, these might indicate bowel obstruction (Carpenito-Moyet, 2009). Decreased output of ostomy effluent might suggest it as well (Carpenito-Moyet, 2009). Monitoring of quantity and consistency of faecal discharges would be helpful to understand Mrs. Lane's condition.

Assessment regarding possible metastasis

The most common site of distant metastasis is the liver and then lungs for colorectal cancer. Since patients after curative surgery are still at risk developing metastasis, nurses should check for palpable abdominal mass, distension, and hepatomegaly.

Conclusion

Colorectal cancer is developed through a multistep course involving accumulated mutations, enhanced by risk factors such as age, genetic inheritance and lifestyle choices. If clinicians could accurately understand pathophysiology of colorectal cancer and its potential influence over body systems, it would be much easier to comprehend surgical and chemotherapeutic procedures, and this might eventually lead to better treatment of Mrs. Lane. Knowledge about how to assess postoperative signs and symptoms is also important to address possible complications or toxicities, and to ensure that Mrs. Lane relieves pain associated with cancer and regains comfortable feelings. Additionally, Mrs. Lane might need intense emotional support as well, since experiencing and surviving cancer would change her life drastically, for example, having to adjust to colostomy. In conclusion, nurses could successfully carry out colorectal cancer treatments with obtaining thorough knowledge in biology, assessment skills to deal with objective and subjective data from patients and understanding special needs of patients.

References